Association of Soluble B7-H4 and Circulating Tumor Cells in Blood of Advanced Epithelial Ovarian Cancer Patients

IntroductionEpithelial ovarian cancer (EOC) is the deadliest gynecologic malignancy worldwide. Reliable predictive biomarkers are urgently needed to estimate the risk of relapse and to improve treatment management. Soluble immune-checkpoints in EOC are promising molecules serving as prognostic biomarkers accessible via liquid biopsy. We thus, aimed at elucidating the role of sB7-H4 in EOC.Material and MethodsWe analyzed soluble serum B7-H4 (sB7-H4) using ELISA and circulating tumor cells (CTCs) in blood applying the AdnaTest OvarianCancer in 85 patients suffering from advanced EOC. Findings were correlated with clinical parameters as well as survival data.ResultssB7-H4 was detectable in 14.1% patients, CTCs in 32.9% patients and simultaneous presence of CTCs and sB7-H4 was found in 7% patients, respectively. Although no association between sB7-H4 and CTC could be documented, each of them served as independent predictive factors for overall survival (OS).ConclusionsB7-H4 and CTCs are independent prognostic biomarkers for impaired survival in EOC. As they are easily accessible via liquid biopsy, they may be of potential benefit for the prediction of therapy response and survival for EOC patients.

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Comparison of Genetic Profiling between Primary Tumor and Circulating Tumor Cells Captured by Microfluidics in Epithelial Ovarian Cancer: Tumor Heterogeneity or Allele Dropout?

Diagnostics ◽

10.3390/diagnostics11061102 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1102

Author(s):

Ting-Yu Chang ◽

Sheng-Wen Chen ◽

Wen-Hsiang Lin ◽

Chung-Er Huang ◽

Mark I. Evans ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Detection ◽

Epithelial Ovarian Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Primary Tumor ◽

Liquid Biopsy ◽

Tumor Heterogeneity ◽

Allele Dropout ◽

Cancer Management

Epithelial ovarian cancer (EOC) is a leading cause of cancer mortality among women but unfortunately is usually not diagnosed until advanced stage. Early detection of EOC is of paramount importance to improve outcomes. Liquid biopsy of circulating tumor cells (CTCs) is emerging as one of the promising biomarkers for early detection of solid tumors. However, discrepancies in terms of oncogenomics (i.e., different genetic defects detected) between the germline, primary tumor, and liquid biopsy are a serious concern and may adversely affect downstream cancer management. Here, we illustrate the potential and pitfalls of CTCs by presenting two patients of Stage I EOC. We successfully isolated and recovered CTCs by a silicon-based nanostructured microfluidics system, the automated Cell RevealTM. We examined the genomics of CTCs as well as the primary tumor and germline control (peripheral blood mononuclear cells) by whole exome sequencing. Different signatures were then investigated by comparisons of identified mutation loci distinguishing those that may only arise in the primary tumor or CTCs. A novel model is proposed to test if the highly variable allele frequencies, between primary tumor and CTCs results, are due to allele dropout in plural CTCs or tumor heterogeneity. This proof-of-principle study provides a strategy to elucidate the possible cause of genomic discrepancy between the germline, primary tumor, and CTCs, which is helpful for further large-scale use of such technology to be integrated into clinical management protocols.

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Development and Validation for Prognostic Nomogram of Epithelial Ovarian Cancer Recurrence based on Circulating Tumor Cells and Epithelial–Mesenchymal Transition

10.21203/rs.3.rs-86051/v2 ◽

2020 ◽

Author(s):

Jiani Yang ◽

Jun Ma ◽

Yue Jin ◽

Shanshan Cheng ◽

Shan Huang ◽

...

Keyword(s):

Ovarian Cancer ◽

Risk Stratification ◽

Epithelial Ovarian Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Epithelial Mesenchymal Transition ◽

Ca 125 ◽

Mesenchymal Transition ◽

Cox Regression Analysis ◽

Significant Difference

Abstract We aimed to determine prognosis value of circulating tumor cells(CTCs) undergoing epithelial–mesenchymal transition(EMT) in epithelial ovarian cancer(EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan–Meier analysis among training group(n=114) and validation group(n=38). By regression screening, both CTC counts(HR 1.187; 95%CI 1.098-1.752; p=0.012) and M-CTC(HR 1.098; 95%CI 1.047-1.320; p=0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites and CA-125 were also collected(p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive value for nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts(p=0.0241), M-CTC(p=0.0107) and the nomogram(p=0.0021) were drawn with significant difference. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration: Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016

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